Skip to main content
SpringerLink
Log in

The 9L rat brain tumor model for pre-clinical investigation of radiation-chemotherapy interactions

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Summary

The rat 9L gliosarcoma brain tumor model has been used for more than thirty years to investigate a variety of potential therapeutic agents, combinations, schedules, and approaches that might be applicable to the management of high-grade malignant brain tumors in man. When tumor cells are implanted intracerebrally, a solid tumor grows until its mass results in the death of the animal, typically between 20 and 30 days post-inoculation. Radiation therapy (either single or fractionated doses) is effective at prolonging survival in a dose-dependent manner. Numerous cancer chemotherapeutic agents, by a variety of doses, schedules, and routes of delivery, have demonstrated therapeutic efficacy in the 9L model. The combination of radiation and agents such as AZQ, BCNU, bleomycin, and cis-platinum has resulted in prolongation of survival that is significantly better than either agent used alone, without exceeding the tolerance of critical normal tissues. These pre-clinical data suggest that combining standard fractionated radiation therapy with appropriate concomitant cytotoxic chemotherapeutic agents might benefit patients with high-grade brain tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Morantz RA, Walsh J (eds): Brain Tumors: A Comprehensive Text, Marcel Dekker, Inc.: New York, 1993

    Google Scholar 

  2. Walker MD, Alexander Jr E, Hunt WE, MacCarty CS, Mahaley MS, Mealey J, Norrell HA, Owens G, Ransohoff J, Wilson CB, Gehan EA, Strike TA: Evaluation of BCNU and/or radiation therapy in the treatment of anaplastic gliomas, a cooperative clinical trial. J Neurosurg 49: 333–343, 1978

    PubMed  Google Scholar 

  3. Levin VA, Silver P, Hannigan J, Wara WM, Gutin PH, Davis RL, Wilson CB: Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int J Radiat Oncol Biol Phys 18: 321–324, 1990

    PubMed  Google Scholar 

  4. Walker MD, Greed SB, Byar DP: Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. New Engl J Med 303: 1323–1329, 1980

    PubMed  Google Scholar 

  5. Barker M, Hoshino T, Gurcay O, Wilson CB, Nielsen SL, Downie R, Eliason J: Development of an animal brain tumor model and its response to therapy with I,3-bis(2-chloroethyl)-I-nitrosourea. Cancer Res 33: 976–986, 1973

    PubMed  Google Scholar 

  6. Weizsaecker M, Deen DF, Rosenblum ML, Hoshino T, Gutin PH, Barker M: The 9L rat brain tumor: description and application of an animal model. J Neurol 224: 183–192, 1981

    PubMed  Google Scholar 

  7. Schmidek HH, Nielsen SL, Schiller AL, Messer J: Morphological studies of rat brain tumors induced by N-nitrosomethylurea. J Neurosurg 34: 335–340, 1971

    PubMed  Google Scholar 

  8. Henderson SD, Kimler BF, Morantz RA: Radiation therapy of 9L rat brain tumors. Int J Radiat Oncol Biol Phys 7: 497–502, 1981

    PubMed  Google Scholar 

  9. Douple EB, Richmond RC, Logan ME: Therapeutic potentiation in a mouse mammary tumor and an intracerebral rat brain tumor by combined treatment with cis-dichlorodiammineplatinum II and radiation. J Hematol Oncol 7: 585–603, 1977

    Google Scholar 

  10. Barker M, Deen DF, Baker DG: BCNU and X-ray therapy of intracerebral 9L rat tumors. Int J Radiat Oncol Biol Phys 5: 1581–1583, 1979

    PubMed  Google Scholar 

  11. Olson JJ, Friedman R, Orr K, Delaney T, Oldfield EH: Enhancement of the efficacy of x-irradiation by pentobarbital in a rodent brain-tumor model. J Neurosurg 72: 745–748, 1990

    PubMed  Google Scholar 

  12. Kimler BF, Liu C, Evans RG, Morantz RA: Pentobarbital may protect the normal brain but not alter the response of the 9L rat brain tumor to radiation therapy. J Neurosurg 79: 577–583, 1993

    PubMed  Google Scholar 

  13. Teicher BA, Holden SA, Ara G, Sotomayor EA, Menon K, Tarbell NJ, Sallan SE: Etanidazole as a modulator of combined modality therapy in the rat 9L gliosarcoma. Int J Oncol 1: 625–630, 1992

    Google Scholar 

  14. Kimler BF, Liu C, Evans RG, Morantz RA: Intracerebral chemotherapy in the 9L rat brain tumor model. J Neurocol 14: 191–200, 1992

    Google Scholar 

  15. Kimler BF, Liu C, Evans RG, Morantz RA: Combination of aziridinylbenzoquinone and cis-platinum with radiation therapy in the 9L rat brain tumor model. Int J Radiat Oncol Biol Phys 26: 445–450, 1993

    PubMed  Google Scholar 

  16. Recht L, Fram RJ, Strauss G, Fitzgerald TJ, Liepman M, Lew R, Kadish S, Sherman D, Wilson J, Greenberger J, Silver D: Preirradiation chemotherapy of supratentorial malignant primary brain tumors with intracarotid cis-platinum (CDDP) and i.v. BCNU. A phase II trial. Am J Clin Oncol 13: 125–131, 1990

    PubMed  Google Scholar 

  17. EORTC Brain Tumor Group: Cisplatin does not enhance the effect of radiation therapy in malignant gliomas. Eur J Cancer 27: 568–571, 1991

    Google Scholar 

  18. Dropcho EJ, Rosenfeld SS, Morawetz RB, Vitek J, Brothers M, Gorum T, Bell S, Gillespie GY, Glantz M, Mahaley MS Jr, Schold SR Jr: Preradiation intracarotid cisplatin treatment of newly diagnosed anaplastic gliomas. The CNS Cancer Consortium. J Clin Oncol 10: 452–458, 1992

    PubMed  Google Scholar 

  19. Mortimer JE, Crowley J, Eyre H, Weiden P, Eltringham J, Stuckey WJ: A phase II randomized study comparing sequential and combined intraarterial cisplatin and radiation therapy in primary brain tumors. A Southwest Oncology Group study. Cancer 69: 1220–1223, 1992

    PubMed  Google Scholar 

  20. Levin VA, Kabra P: Effectiveness of the nitrosoureas as a function of lipid solubility for the chemotherapy of experimental rat brain tumors. Cancer Chemother Rept 58: 787–792, 1974

    Google Scholar 

  21. Wheeler KT, Kaufman K, Feldstein M: Response of a rat brain tumor to fractionated therapy with low doses of BCNU and irradiation. Int J Radiat Oncol Biol Phys 5: 3–1557, 1979

    Google Scholar 

  22. Wheeler KT, Kaufman K: Influence of fractionation schedules on the response of a rat brain tumor to therapy with BCNU and radiation. Int J Radiat Oncol Biol Phys 6: 845–849, 1980

    PubMed  Google Scholar 

  23. Wheeler KT, Kaufman K: Efficacy of continuous treatment with radiation in a rat brain-tumor model. J Neurosurg 55: 52–54, 1981

    PubMed  Google Scholar 

  24. Wheeler KT, Kaufman K: Brain tumor therapy: prospects for combining BCNU with conventional radiotherapy schedules. Int J Radiat Oncol Biol Phys 7: 1065–1068, 1981

    PubMed  Google Scholar 

  25. Gutin PH, Bernstein M, Sano Y, Deen DF: Combination therapy with 1,3-bis(2-chloroethyl)-I-nitrosourea and low dose rate radiation in the 9L rat brain tumor and spheroid models: implications for brain tumor brachytherapy. Neurosurgery 15: 781–786, 1984

    PubMed  Google Scholar 

  26. Spence AM, Geraci JP: Combined cyclotron fast-neutron and BCNU therapy in a rat brain-tumor model. J Neurosurg 54: 461–467, 1981

    PubMed  Google Scholar 

  27. Nakamura O, Matsutani M, Nomura K, Shitara N, Takakura K, Ishizaki R: Treatment of autochthonous rat brain tumors with chemotherapy and radiotherapy. Gan To Kagaku Ryoho 14: 1069–1074, 1987

    PubMed  Google Scholar 

  28. Shapiro WR, Green SB, Burger PC, Mahaley MS Jr, Selker RG, VanGlider JC, Robertson JT, Ransohoff J, Mealey J Jr, Strike TA, Pistenmaa DA: Randomized trial of three chemotherapy regimens and two radiotherapy regimens in postoperative treatment of malignant glioma. J Neurosurg 71: 1–9, 1989

    Google Scholar 

  29. Salazar OM, VanHoutte PJ, Bennet JM, Rubin P, Wheeler KT: High-dose radiation therapy with low-dose (pulsed) BCNU in malignant gliomas: an Eastern Cooperative Oncology Group (ECOG) report. Int J Radiat Oncol Biol Phys 8: 915–919, 1982

    PubMed  Google Scholar 

  30. Henderson SD, Kimler BF, Barnes ML: Comparison of cancer chemotherapeutic agents in asynchronous and synchronous 9L cells. Invest New Drugs 5: 145–154, 1987

    PubMed  Google Scholar 

  31. Vats TS, Morantz RA, Wood GW, Tilzer S: Study of effectiveness of bleomycin in rat brain tumor model intravenously and intracerebrally. Int J Radiat Oncol Biol Phys 5: 1527–1529, 1979

    PubMed  Google Scholar 

  32. Morantz RA, Kimler BF, Vats TS, Henderson SD: Bleomycin and brain tumors: a review. J Neuro-Oncology 1: 249–255, 1983

    Google Scholar 

  33. Kimler BF, Vats TS, Morantz RA, Henderson SD: Response of the 9L rat brain tumor to combination treatment with radiation and bleomycin. Int J Radiat Oncol Biol Phys 7: 1069–1074, 1981

    PubMed  Google Scholar 

  34. Kimler BF, Martin DF, Evans RG, Morantz RA, Vats TS: Combination of radiation therapy and intracranial bleomycin in the 9L rat brain tumor model. Int J Radiat Oncol Biol Phys 18: 1115–1121, 1990

    PubMed  Google Scholar 

  35. Kristiansen K, Hagen S, Kollevold T, Torvik A, Holme I, Nesbakken R, Hatlevoll R, Lindgren M, Brun A, Lindgren S, Notter G, Andersen AP, Eigen K: Combined modality therapy of operated astrocytomas grade III and IV. Confirmation of the value of post-operative irradiation and lack of potentiation of Bleomycin on survival time. Cancer 47: 649–652, 1981

    PubMed  Google Scholar 

  36. Halperin EC, Gaspar L, Imperato J, Salter M, Herndon J 2d, Dowling S: An analysis of radiotherapy data from the CNS cancer consortium's randomized prospective trial comparing AZQ to BCNU in the treatment of patients with primary malignant brain tumors. The CNS cancer consortium. Am J Clin Oncol 16: 277–283, 1993

    PubMed  Google Scholar 

  37. Kimler BF, Martin DF, Evans RG, Morantz RA, Vats TS: Effects of spirogermanium and radiation therapy in the 9L rat brain tumor model. NCI Monogr 6: 115–118, 1988

    PubMed  Google Scholar 

  38. Furuta T, Fujiwara T, Rosenfeld SA, Wilkinson HA: Synergistic effect of methotrexate and radiation on gliosarcoma in tissue culture and in rats. Neurosurgery 18: 596–603, 1986

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. PHd Radiation Biology Laboratory, Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, KS, USA

    Bruce F. Kimler

Authors
  1. Bruce F. Kimler
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kimler, B.F. The 9L rat brain tumor model for pre-clinical investigation of radiation-chemotherapy interactions. J Neuro-Oncol 20, 103–109 (1994). https://doi.org/10.1007/BF01052721

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01052721

Key words

Search

Navigation